Organ dysfunction caused by sepsis is life-threatening and results in high mortality. Therapeutic options for sepsis are limited. Pathogenic factors are considered as components of environmental pressure that modify DNA methylation patterns thereby enhancing disease progression. Here, we found that sepsis patients exhibited higher levels of genomic DNA methylation patterns and hypermethylated genes associated with the NF-kB signaling pathway. Therefore, we hypothesized that a DNA methyl transferase inhibitor, Decitabine, may mitigate inflammation and improve survival by inhibiting the NF-κB signaling pathway. To test the hypothesis, mice challenged with caecal ligation and puncture (CLP) were subcutaneously injected with Decitabine solution (0.5, 1, and 1.5 mg/kg) 2 h following operation. Our results indicated that Decitabine reduces DNA methyltransferases (DNMTs), attenuates NF-κB activation, downregulates inflammatory cytokine levels, and inhibits the progression of sepsis. Thus, DNA methylation may be indispensable for sepsis and serve as a predicting factor. The use of Decitabine could represent a novel strategy in the treatment of sepsis.

由败血症引起的器官功能障碍危及生命，并导致高死亡率。败血症的治疗选择有限。致病因素被认为是改变DNA甲基化模式从而增强疾病进展的环境压力的组成部分。在这里，我们发现败血症患者表现出更高水平的基因组DNA甲基化模式和与NF-kB信号通路相关的超甲基化基因。因此，我们假设DNA甲基转移酶抑制剂地他滨可以通过抑制NF-κB信号传导途径减轻炎症并提高生存率。为了验证这一假设，在手术后2小时，将接受盲肠结扎和穿刺（CLP）攻击的小鼠皮下注射地西他滨溶液（0.5、1和1.5 mg / kg）。我们的结果表明，地西他滨可降低DNA甲基转移酶（DNMT），减弱NF-κB活化，下调炎症细胞因子水平并抑制败血症的进展。因此，DNA甲基化可能是败血症必不可少的，并可以作为预测因素。地西他滨的使用可能代表了败血症治疗的新策略。